In the adult rat septo-hippocampal model for acute experimental lesions, a complete transection of the fimbria fornix causes the ipsilateral disappearance of most of the medial septum cholinergic (MSC) neurons. The apparent loss of MSC neurons is prevented by continuous intraventricular infusion of Nerve Growth Factor (NGF), and is largely reversed by delayed NGF treatments. In addition, NGF treatments cause an increase in body size and ChAT immunostaining in cholinergic neurons of an undamaged neostriatum. This proposal has two major aims. One is to expand-our still modest information concerning the action of NGF on adult cholinergic neurons by, for example, defining dose-responsive relationships, understanding the limits of a delayed NGF rescue, identifying additional responses to NGF with or without experimental lesions. and evaluating chronic cholinergic deficits upon treatment with NGF antibodies. The other is to examine the ability of selected agents other than NGF, alone or in surgery with NGF, to elicit responses from cholinergic and other adult CNS neurons. The actions of NGF on adult mammalian CNS cholinergic neurons provide the first direct evidence of the more general roles that neuronotrophic factors are likely to play in maintenance and repair of central neurons and the opportunities that these factors may represent for new therapeutic approaches to human CNS degeneration disorders and for human brain and spinal cord lesions.